Tremelimumab Failure in Mesothelioma Trial Highlights Week in Cancer News

Recent advances and updates in oncology and cancer drug development.

Obinutuzumab Approved for Follicular Lymphoma

The FDA approved obinutuzumab plus bendamustine followed by obinutuzumab alone for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen, according to Genentech, the manufacturer of the anti-CD20 agent. The approval was based on the phase III GADOLIN study, in which obinutuzumab plus bendamustine followed by obinutuzumab monotherapy reduced the risk of disease progression by 52% compared with bendamustine alone (HR, 0.48; P <.0001) in patients with follicular lymphoma who progressed on rituximab-based therapy.

The median progression-free survival, as determined by an independent panel, was not reached in the obinutuzumab arm versus 13.8 months in the control arm. By investigator assessment, the median PFS with obinutuzumab was 29.2 months versus 13.7 months with bendamustine alone (HR, 0.48; P <.0001). At a median follow-up of 24.1 months, the risk of death was reduced by 38% with the obinutuzumab regimen compared with bendamustine alone (HR, 0.62; 95% CI, 0.39-0.98). Median overall survival had not yet been achieved. Response rates were similar between the two groups.

See more at: http://www.onclive.com/web-exclusives/fda-approves-obinutuzumab-for-follicular-lymphoma

Everolimus Approved for GI, Lung NETs

The FDA has approved everolimus for the treatment of adult patients with progressive, well-differentiated non-functional, locally advanced or metastatic gastrointestinal or lung neuroendocrine tumors, based on findings from the phase III RADIANT-4 trial. In the study, median progression-free survival was 11 months with the mTOR inhibitor versus 3.9 months for placebo, representing a 52% reduction in the risk of progression or death (HR, 0.48; P <.001).

Median PFS by investigator assessment with everolimus was 14.0 versus 5.5 months with placebo (HR, 0.39; P <.001). A preplanned interim OS analysis performed after 37% of events showed an early 36% reduction in the risk of death with everolimus (HR, 0.64; 95% CI, 0.40—1.05); however, the OS difference had not yet achieved (P = .037). The FDA approved everolimus in May 2011 as a treatment for patients with progressive, metastatic pancreatic NETs. This decision was based on a similar positive demonstration of efficacy in the phase III RADIANT-3 study.

See more at: http://www.onclive.com/web-exclusives/fda-approves-everolimus-for-gi-lung-nets

Phase III Trial of Bavituximab in NSCLC Stopped

The phase III SUNRISE trial comparing bavituximab plus docetaxel with docetaxel and placebo for patients with non—small cell lung cancer has been halted following a futility analysis, according the developer of the anionic phospholipids inhibitor, Peregrine Pharmaceuticals. At the prespecified analysis that was conducted after 33% of events, an Independent Data Monitoring Committee found that the combination of bavituximab and docetaxel failed to improve overall survival compared with docetaxel and placebo.

In the study, the bavituximab combination showed OS data similar to expectations while patients in the docetaxel-alone arm “dramatically outperformed OS expectations,” according to Peregrine. While data from SUNRISE are analyzed, Peregrine announced that it would be placing its other bavituximab/chemotherapy combination studies on hold. Trials exploring bavituximab with immunotherapy are still being conducted as planned. A phase II study is currently being designed to assess the PD-L1 inhibitor durvalumab with or without bavituximab for patients with metastatic NSCLC.

See more at: http://www.onclive.com/web-exclusives/peregrine-stops-phase-iii-trial-of-bavituximab-in-nsclc

New Data Under Review for Enzalutamide in Prostate Cancer

The FDA has accepted a supplemental new drug application for enzalutamide capsules as a treatment for patients with metastatic castration-resistant prostate cancer. The new application includes findings from the head-to-head studies, TERRAIN and STRIVE. The sNDA updates the section of the label that discusses the clinical studies; however, changes in the indication are not being sought.

In the 375-patient TERRAIN study, the median PFS for patients in the enzalutamide arm was 15.7 months compared with 5.8 months for patients who received bicalutamide (HR, 0.44; 95% CI, 0.34-0.57). The median time to PSA progression was 19.4 months with enzalutamide versus 5.8 months with bicalutamide (HR, 0.28). In the 396-patient STRIVE trial, the median PFS was 19.4 months in patients treated with enzalutamide and 5.7 months in those given bicalutamide.

In those with M1 disease (n = 257), the median PFS was 16.5 months with enzalutamide and 5.5 months with bicalutamide. The Prescription Drug User Fee Act goal date for a decision on the sNDA is set for October 22, 2016.

See more at: http://www.onclive.com/web-exclusives/fda-agrees-to-review-supplemental-nda-for-enzalutamide-in-metastatic-prostate-cancer

Tremelimumab Strikes Out in Mesothelioma

Second- or third-line treatment with tremelimumab monotherapy failed to improve overall survival for patients with unresectable malignant mesothelioma, according to topline results from the phase IIb DETERMINE trial released by the developer of CTLA-4 inhibitor, AstraZeneca. Data from the study, which enrolled 571 patients with unresectable pleural or peritoneal malignant mesothelioma, are being prepared for presentation at an upcoming medical meeting.

Prior to the disappointing results, the agent had been granted an orphan drug designation for malignant mesothelioma. In a 29-patient study of tremelimumab in mesothelioma, the objective response rate was 6.9% and the duration of response was 12.4 months. The median OS was 10.7 months and the median progression-free survival was 6.2 months. The 1-year OS rate was 48.3% and the 2-year OS rate was 36.7%. In addition to CTLA-4 inhibitors, the PD-1/PD-L1 agents have also shown promise in mesothelioma.

A phase II study is exploring durvalumab plus tremelimumab in surgically resectable malignant pleural mesothelioma.

See more on immune checkpoint inhibitors in mesothelioma and small cell lung cancer here: http://www.onclive.com/conference-coverage/NYL-2015/checkpoint-inhibitors-show-promise-for-sclc-mesothelioma

See more on the failed trial http://www.onclive.com/web-exclusives/tremelimumab-misses-os-endpoint-in-phase-iib-mesothelioma-trial